Senolytics are compounds that target and remove senescent cells - damaged cells that stop dividing but linger in the body, causing inflammation and contributing to aging and diseases like cancer, diabetes, and Alzheimer's. By clearing these cells, senolytics aim to improve health and potentially extend lifespan. Here's what you need to know:
- What are senescent cells? These are damaged cells that stop dividing but release harmful inflammatory molecules, harming nearby tissues.
- Why are senolytics important? They selectively remove senescent cells, reducing inflammation and improving cardiovascular, immune, and brain health.
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Key senolytics:
- Dasatinib + Quercetin (D+Q): A powerful combination for clearing senescent cells.
- Fisetin: A natural compound found in strawberries and apples, known for its safety and anti-inflammatory effects.
- Emerging therapies: Advanced approaches like CAR-T cells, antibody-drug conjugates, and AI-designed molecules are being developed for precision targeting of senescent cells.
- Benefits: Studies show senolytics can improve blood vessel health, strengthen the immune system, and enhance cognitive function.
- Risks: Potential side effects include fatigue, gastrointestinal discomfort, and, for some synthetic senolytics, more serious risks like low platelet counts.
Quick Summary
Senolytics offer a promising approach to address aging at its root by removing harmful senescent cells. While they show potential to improve healthspan and reduce age-related diseases, careful research and medical guidance are essential to manage risks and optimize benefits.
Ageing, Cellular Senescence and Senolytics: The Path to Translation | Prof James Kirkland
Main Senolytic Compounds and How They Work
Senolytic compounds are designed to target and remove harmful senescent cells, which play a significant role in aging. These compounds use various mechanisms to achieve this, often working together to enhance their effects.
Dasatinib and Quercetin (D+Q)
The combination of dasatinib and quercetin is one of the most researched senolytic therapies. Dasatinib, a tyrosine kinase inhibitor approved by the FDA, promotes the programmed death (apoptosis) of senescent cells. Quercetin, a natural flavonoid, complements this by offering antioxidant and anti-inflammatory benefits, which help suppress the harmful effects of the senescence-associated secretory phenotype (SASP). Together, they create a powerful synergy: dasatinib triggers cell death, while quercetin disrupts the cells' ability to survive. Studies have shown that this duo can effectively clear senescent cells, reduce fat buildup, and lower the expression of fibrosis-related genes [2][3].
Fisetin: A Natural Senolytic
Fisetin, a naturally occurring senolytic, is found in foods like strawberries (160 µg/g), apples (27 µg/g), and onions (5 µg/g). It works by targeting senescent cells through multiple pathways, leading to their apoptosis [5]. However, the amount of fisetin typically consumed through diet - about 0.4–0.8 mg - is far below the levels needed for therapeutic effects [5].
Fisetin stands out for its safety in humans and its potential to deliver meaningful health benefits, even when introduced later in life [4]. Research has shown that fisetin can reduce artery stiffness, with effects comparable to those of the synthetic senolytic ABT-263 [7]. It is widely considered one of the safest and most effective natural senolytics [6].
MASI Longevity Science has developed pharmaceutical-grade fisetin formulations to address challenges like low bioavailability and rapid metabolism [5]. These advanced formulations are designed to improve absorption, supporting the body's natural ability to renew cells and align with MASI’s science-driven focus on longevity.
Other New Senolytic Compounds
Senolytic research is moving beyond repurposed drugs, exploring innovative techniques like CAR-T cells, antibody-drug conjugates (ADCs), and vaccine-based strategies. These emerging methods aim to target senescent cells with greater precision. Artificial intelligence is also playing a critical role in identifying new and effective senolytic molecules [1].
ADCs, for example, deliver toxic drugs directly to senescent cells. Research led by Poblocka and colleagues demonstrated that an ADC targeting beta-2 microglobulin eliminated 35% of senescent cells in colon and bladder cancer cell lines [1]. Similarly, CAR-T cell therapy has shown promise: uPAR-targeted CAR-T cells successfully removed senescent cells in liver models, while NKG2D CAR-T cells demonstrated effectiveness across various senescence models [1].
These advanced therapies can be grouped into two categories: stressors, which damage senescent cells, and inhibitors, which block their survival mechanisms [8]. Together, these cutting-edge approaches are expanding the possibilities for long-term cellular health and rejuvenation.
Long-Term Effects of Senolytics on Cellular Health
Years of research have shown that senolytics can lead to lasting benefits for cardiovascular, immune, and cognitive health. Let’s take a closer look at how these treatments impact specific systems over time.
Blood Vessel System Improvements
Cardiovascular disease remains one of the leading causes of death among older adults in the U.S. Long-term senolytic treatments have shown promise in mitigating vascular damage.
A 2016 study from the Mayo Clinic revealed that mice treated with dasatinib and quercetin (D+Q) for three months experienced noticeable improvements in vascular function. While the size of atherosclerotic plaques stayed the same, calcification within the plaques was significantly reduced [9]. Dr. James Kirkland, director of the Robert and Arlene Kogod Center on Aging at Mayo Clinic, highlighted the importance of this finding:
"This is the first evidence that longer term use of senolytic drugs to clear these damaged cells from the body can have a preventative impact against vascular diseases." [9]
Senolytics also improve how blood vessels dilate by enhancing nitric oxide production, which supports endothelial function. In heart tissue, these treatments may help combat or even reverse cardiac fibrosis - a type of scarring linked to age-related heart conditions. A 2020 study demonstrated that navitoclax treatment in mice after heart injury reduced senescent cells, improved heart function, promoted new blood vessel growth, and decreased scar tissue size [10]. Dr. Jordan Miller, a cardiovascular researcher at Mayo Clinic, emphasized the significance of these findings:
"Our finding that senolytic drugs can reduce cardiovascular calcification is very exciting, since blood vessels with calcified plaques are notoriously difficult to reduce in size, and patients with heart valve calcification currently do not have any treatment options other than surgery." [9]
Immune System Changes
Senolytics also bring critical benefits to the immune system, which naturally weakens with age. Older adults face declining immune responses and increased inflammation, leaving them more vulnerable to infections and less responsive to vaccines [11]. With the elderly population expected to triple by 2050 [11], addressing this issue has become increasingly important.
Studies in older mice have shown that treatments like fisetin, D+Q, or genetic removal of senescent cells can cut mortality rates by about 50% when exposed to common pathogens [11]. These therapies may also improve vaccine efficacy in older individuals, countering the weaker antibody and T-cell responses typically seen in this demographic [11]. However, senolytics aren’t without risks. For example, dasatinib has been associated with viral reactivation in some patients, suggesting that different senolytic drugs may come with unique immune-related side effects [11]. There’s also evidence that while senolytics can strengthen primary immune responses, they might negatively impact immunological memory [12].
Brain and Cognitive Effects
Senolytics offer promising benefits for brain health, particularly by reducing inflammation that disrupts neuronal function.
In February 2025, a pilot study provided the first human evidence of cognitive improvements from senolytic treatments. Researchers at Hebrew SeniorLife administered dasatinib (100 mg) and quercetin (1,250 mg) to 12 participants with mild cognitive impairment. The regimen - two days every two weeks for 12 weeks - led to a statistically significant 2.0-point increase on the Montreal Cognitive Assessment (MoCA) for those with the lowest baseline scores [13]. The study also found that reductions in tumor necrosis factor alpha (TNF-α) were linked to these cognitive gains [13]. Dr. Courtney L. Millar from Hebrew SeniorLife noted:
"Our findings suggest that senolytic treatment with dasatinib and quercetin is well-tolerated in older adults at risk for Alzheimer's disease and may improve cognition by targeting the harmful effects of cellular senescence." [13]
Animal studies further support these findings. Long-term senolytic treatments have been shown to preserve the integrity of the blood-brain barrier and improve hippocampal synaptic function, which is vital for memory [14]. Additionally, these treatments reduced markers of neuroinflammation and senescence-associated gene expression in the spleen [14]. This suggests that clearing senescent cells throughout the body can reduce inflammation affecting the brain, even if the drugs don’t directly cross the blood-brain barrier.
Taken together, the long-term benefits of senolytics across cardiovascular, immune, and neurological systems highlight their potential to combat aging at its core, promoting both a longer and healthier life through cellular renewal.
Weighing Risks and Benefits of Senolytic Therapy
Senolytics hold promise for improving health and extending lifespan, but like any medical intervention, they come with potential risks. Understanding these risks and how to manage them is essential for anyone considering senolytic therapy.
Safety and Side Effects
The safety of senolytics largely depends on the specific compound and its dosage. Natural options like quercetin and fisetin are generally considered safer but can still cause issues at higher doses [19]. Synthetic senolytics, such as dasatinib and navitoclax, tend to carry more serious risks, including low platelet counts (thrombocytopenia) [19].
Most people report mild side effects like fatigue, headaches, or minor stomach discomfort [15]. Moderate reactions may include nausea, diarrhea, inflammation, or fluctuations in blood pressure [15]. Here's a breakdown of side effects by severity:
| Severity Level | More Common Side Effects | Less Common Side Effects |
|---|---|---|
| High | N/A | Severe allergic reactions, low blood cell counts, liver toxicity, cardiovascular issues, increased infection risk |
| Moderate | Gastrointestinal issues (nausea, diarrhea) | Increased inflammation, blood pressure fluctuations |
| Low | Mild gastrointestinal discomfort, fatigue, headache | Skin rashes, mild allergic reactions |
The long-term effects of senolytic therapy remain unclear [15]. Nicolas Musi, MD, from Cedars-Sinai, highlights this uncertainty:
"Some interventions that target fundamental aging processes could even cause a lot of harm" [16].
Dr. James Kirkland underscores the experimental nature of this field:
"We know 2% of what we need to know. This is a completely new area of medicine. If it works, it would change everything." [16].
Because of these potential risks, careful dosing strategies are critical to balancing benefits and minimizing harm.
Intermittent vs. Continuous Dosing
How often senolytics are taken plays a big role in their safety and effectiveness. Continuous dosing can interfere with the body's natural repair processes. For example, when senolytics continuously target cells expressing p16INK4a and p21, tissue repair can be negatively affected [17]. This happens because some senescent cells actually aid in healing.
Intermittent dosing, on the other hand, appears to strike a better balance. It reduces harmful senescent cells while allowing the body to maintain its ability to heal [17]. Research supports this approach: in animal studies, intermittent dasatinib and quercetin (D+Q) dosing accelerated bone fracture recovery compared to continuous dosing [17]. Similarly, a short three-day treatment with D+Q improved lung function in injury models when administered two weeks after the injury [17].
Continuous dosing has shown clear drawbacks. For instance, in skin wound studies, six days of continuous ganciclovir delayed healing [17]. Likewise, two weeks of continuous D+Q treatment impaired lung epithelial stem cell regeneration [17]. Intermittent dosing not only preserves tissue repair but also reduces side effects [20]. Since senolytics don’t require constant exposure to work, continuous use offers no extra benefits and increases risks [20].
Biomarker-Guided Treatment
Personalized approaches using biomarkers are emerging as a way to refine senolytic therapy. While no single marker can definitively identify senescent cells, researchers use a combination of indicators to improve accuracy [21]. These include physical changes in cells, DNA damage responses, proteins like p16INK4a and p21, and inflammatory markers such as IL-6 [21]. Detection methods range from microscopy to advanced tools like flow cytometry and genetic analysis [21].
Early trials are already showing how biomarkers can guide treatment. For example, in a phase 1 trial of dasatinib and quercetin for early Alzheimer's disease, researchers tracked biomarkers in blood, cerebrospinal fluid, and urine [22]. They observed increases in plasma fractalkine and MMP-7, along with cerebrospinal fluid IL-6 levels after treatment [22]. Additionally, inflammatory genes such as FOS, FOSB, IL1β, IL8, JUN, JUNB, and PTGS2 were downregulated in blood cells [22]. While these changes suggest senolytics are working at a cellular level, interpreting these results requires expertise due to the complexity of senescent cells.
The bottom line is clear: senolytic therapy should always be approached with professional medical guidance. Dr. Kirkland's advice is a valuable reminder:
"People have to be very, very concerned about what they buy. Don't take advice over the internet and pay exorbitant prices for things that may or may not work." [16].
Healthcare providers can customize treatment by monitoring biomarkers and adjusting doses based on individual responses [15]. This is particularly important for certain groups - like pregnant women - who should avoid senolytics entirely [18].
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MASI Longevity Science: Supporting Cellular Health
MASI Longevity Science is exploring the potential of natural compounds to promote cellular renewal, drawing from the growing field of senolytics. Compounds like fisetin and resveratrol are at the forefront of their efforts, aiming to support cellular health and longevity. By focusing on these natural ingredients, MASI seeks to translate the promise of senolytic therapies into practical solutions for cellular rejuvenation.
Fisetin and Resveratrol for Senescent Cell Clearance
MASI's approach to cellular health revolves around two powerful compounds: fisetin and resveratrol. Research highlights their ability to combat cellular senescence by reducing markers like p53 and p38MAPK, while also lowering SASP (senescence-associated secretory phenotype) markers such as MMP-9 and MMP-13, as well as inflammatory mediators like IL-1β, TGF-β, and IL-6 [23].
MASI offers a Premium Fisetin (500 mg) formulation, which acts as an antioxidant and helps remove aged cells by influencing inflammation, apoptosis, and autophagy [24]. This is complemented by Premium Resveratrol (500 mg), which works in tandem with fisetin to further suppress p53 and reduce the harmful effects of SASP. With osteoarthritis affecting about 52.3 million adults in the U.S. - a number projected to climb to 67 million by 2030 [23] - these compounds offer a promising avenue for maintaining joint and cellular health.
Quality and Safety Standards
MASI prioritizes quality and safety through rigorous production and testing. Their supplements are manufactured in a cutting-edge facility in Germany and undergo independent testing in Switzerland to ensure top-tier standards [25]. The products are designed to meet a wide range of dietary needs: they are vegan-friendly, Halal and Kosher certified, and free from GMOs, soy, lactose, gluten, and common allergens. Dosage guidelines are tailored to different age groups, recommending one capsule daily for individuals aged 40–50 and two capsules daily for those over 50 [25].
Science-Based Formulations for Longevity
MASI's products are deeply rooted in cutting-edge research, developed in collaboration with leading longevity experts. Their formulations are designed to target key aging mechanisms while addressing challenges like achieving effective intracellular concentrations. Collaborating with experts from institutions such as Harvard Medical School and the Mayo Clinic, MASI creates premium supplements using German-sourced materials, with every batch undergoing rigorous testing in Switzerland [25].
The product lineup includes Premium NMN (1,000 mg), Premium Resveratrol (500 mg), Premium Spermidine (3 mg), and Premium Fisetin (500 mg) [25]. These carefully crafted formulations reflect MASI's commitment to turning scientific advancements into practical tools for enhancing longevity and cellular health.
The Future of Senolytics in Aging
The Promise of Senolytics
As populations age and chronic illnesses become more prevalent, there’s an urgent need for solutions that address aging at its root. By 2050, the number of people aged 80 and older is expected to reach 426 million - three times the number in 2020 [26]. Today, over 90% of individuals aged 65 and above live with at least one chronic disease, and more than 70% manage two or more [29]. Non-communicable chronic diseases are a leading cause of mortality, contributing to 41 million deaths annually and accounting for 71% of global deaths [27].
Senolytic therapies hold great potential to tackle this growing health challenge. Unlike traditional treatments that focus on managing symptoms, senolytics aim to address the root causes of aging by targeting and clearing senescent cells - cells that accumulate as we age and contribute to chronic disease and tissue dysfunction [28].
The field of senolytics is evolving quickly, moving beyond conventional drug repurposing methods, which may have reached their limits [1]. Newer strategies are emerging, including immunological approaches like CAR-T cell therapies, antibody-drug conjugates, and vaccines. Artificial intelligence is also playing a role in identifying entirely new classes of senolytic compounds [1]. For instance, research by Amor et al. demonstrated how CAR T-cells targeting the urokinase-type plasminogen activator receptor (uPAR) could selectively eliminate senescent cells both in laboratory settings and in living organisms. This highlights the potential of precision therapies to combat aging at the cellular level [26].
One of the advantages of targeting senescent cells is their non-dividing nature, which reduces the likelihood of developing drug resistance. Additionally, senotherapeutic agents may help mitigate the negative effects of other aging-related processes [26]. These advancements point to a future where aging interventions are not only more effective but also safer.
MASI Longevity Science and the Path Forward
MASI Longevity Science is bridging the gap between cutting-edge senolytic research and practical, everyday solutions for cellular health. While advanced therapies like CAR-T cells and antibody-drug conjugates are still in development, MASI focuses on natural compounds with established senolytic properties that can be seamlessly integrated into current health regimens.
Their Premium Fisetin and Premium Resveratrol supplements are examples of how senolytic science is being translated into accessible, thoroughly tested products. These formulations are designed to target key cellular pathways, aligning with the scientific push for therapies that are both effective and selective, minimizing potential side effects [1]. With flexible subscription options, MASI makes it easier for individuals to incorporate long-term support for cellular health into their daily lives.
As the global population of older adults continues to grow, taking proactive steps to support cellular health is becoming increasingly important. MASI Longevity Science offers a practical starting point for addressing cellular senescence today, paving the way for even more advanced therapies in the years to come.
FAQs
What are the long-term benefits of senolytics for age-related conditions?
Senolytics represent an emerging category of drugs aimed at eliminating senescent cells - those damaged cells that linger in the body and play a role in aging and chronic illnesses. By clearing these cells, researchers have found that senolytics can help decrease inflammation, boost physical performance, and encourage healthier aging.
There’s also evidence pointing to their potential in tackling age-related conditions like cardiovascular diseases and neurodegenerative disorders. By targeting one of the underlying contributors to aging, senolytics could pave the way for improved vitality and a more sustained, healthier lifespan.
How do new therapies like CAR-T cells and AI-designed molecules improve the ability to target senescent cells compared to traditional senolytics?
Emerging Therapies: CAR-T Cells and AI-Designed Molecules
New approaches like CAR-T cells and AI-designed molecules are changing the game when it comes to targeting senescent cells with precision. CAR-T cells are specially engineered to recognize and eliminate specific markers found on senescent cells. This method offers a highly targeted approach, reducing the risk of unintended effects compared to traditional senolytics. A prime example is the use of NKG2D-CAR T cells, which have shown promise in clearing senescent cells from aging tissues, potentially alleviating age-related conditions.
On the other hand, AI-designed molecules leverage cutting-edge algorithms to discover new senolytic compounds with enhanced specificity. By using advanced computational tools, researchers can identify treatments that are not only more effective but also safer for patients. These breakthroughs are paving the way for more precise and efficient strategies to combat cellular aging, supporting healthier and more resilient aging processes.
What are the key factors and risks to consider when choosing between intermittent and continuous dosing of senolytic compounds?
When choosing between intermittent and continuous dosing of senolytic compounds, it's essential to weigh factors like effectiveness, safety, and potential side effects. Intermittent dosing tends to be the more popular option because it may reduce the chances of side effects, such as myelosuppression - a condition that can arise from extended use of high doses. This method also helps safeguard healthy, non-senescent cells, which play a critical role in tissue repair and regeneration.
In contrast, continuous dosing might interfere with tissue balance or hinder the body’s ability to heal by overly depleting senescent cells. Finding the right dosing strategy is key to maximizing the benefits of senolytics while protecting overall cellular health and function.
